Two Norwegian families illustrating the problem of genotype and phenotype in frontal lobe epilepsy

Abstract

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) was first described in 1994 by Scheffer et al. in one large Australian family (1). This was the first report on a human partial epilepsy syndrome to follow single gene inheritance. A gene locus for ADNFLE has been assigned to the genomic region 20q13.3 by linkage analysis of the Australian family (2). In this family, a mutation causing an amino acid exchange (Ser248Phe) in the second transmembrane domain of the neuronal nicotinic acetylcholine receptor α4 subunit was found. In Norway, we have identified two families with ADNFLE, the first in 1996 and the second in 1999 (3, 4). In the first Norwegian family, there was a different mutation (776ins3) in the same gene than in the Australian family (CHRNA4), inserting an additional leucine residue at the extracellular end of the second transmembrane domain. The second Norwegian family had the same Ser248Phe-mutation as the original Australian family. These findings gave us the unique opportunity to compare the phenotypic expressions of ADNFLE in two families with different mutations in the same gene.